Method for the diagnostic and/or prognostic assessment of acute-on-chronic liver failure syndrome in patients with liver disorders

Abstract

An ex vivo method for the diagnostic and/or prognostic assessment of the acute-on-chronic liver failure (ACLF) syndrome in a patient with a liver disorder, includes measuring a panel of metabolites related with acylcarnitines-sialic acid-acetylated amino acids and amino acid derivatives and/or sugar alcohols, catecholamines and pyrimidine derivatives in a biological sample of the patient, and comparing the level of the metabolites in the sample with the level of the metabolites in healthy patients. An increase of at least 1.2 times of the level of the metabolites is indicative of ACLF syndrome.

1 . An ex vivo method for diagnostic and/or prognostic and treatment of acute-on-chronic liver failure (ACLF) syndrome in a patient with a liver disorder, comprising:
 a) obtaining a biological sample or having a biological sample obtained from said patient;   b) measuring or having measured a level of each of a panel of metabolites selected from the group consisting of acylcarnites, sialic acid, acetylated amino acids and amino acid derivatives and/or sugar alcohols, catecholamines and nucleoside derivatives in the biological sample from the patient;   c) comparing the measured level of each of said metabolites in the sample with a level of each of said metabolites in healthy patients; and   d) determining that the level of a plurality of said metabolites is increased by at least 1.2 times in the patient compared to the level of the plurality of metabolites in the healthy patients, thereby determining that the patient has or is likely to develop the ACLF syndrome:   e) stratifying the patient by prognosis and based on said prognosis providing a treatment selected from the group consisting of:
 i) intensive care treatment alone; 
 ii) emergency transplantation; 
 iii) rengenerative therapy; and 
 iv) bioartificial liver support. 
   
     
     
         2 . The method according to  claim 1 , wherein said acylcarnitines, sialic acid, acetylated amino acids and amino acid derivatives are selected from the group consisting of 2-Heptanone, cystathionine, hexanoylcarnitine, N-Acetylneuraminic acid, N-Acetyl-L-phenylalanine, 2,2′-Thiodiacetic acid, octanoylcarnitine, trisaccharides, hydroxyphenylacetic acids, N6,N6,N6-Trimethyl-L-lysine, N-Acetyl-L-alanine, N-Acetyl-Asp-Glu, N-Acetyl-L-tyrosine, butyrylcarnitine, p-Hydroxyphenyllactic acid, phenylllactic acid, N-Acetyl-L-aspartic acid, L-Saccharopine, Methylimidazoleacetic acid and N-Formyl-L-methionine. 
     
     
         3 . The method according to  claim 1 , wherein said sugar alcohols, catecholamines and nucleoside derivatives are selected from the group consisting of pentose phosphates, pentose alcohols, hexose alcohols, D-Galacturonic acid, beta-Pseudouridine, D-glucuronic acid, 4-Hydroxy-3-methoxyphenylglycol sulfate, D-Threitol, mevalonic acid, orotidine, 5′Deoxy-5′-(methylthio)adenosine, and Guanidinosuccinic acid. 
     
     
         4 . The method according to  claim 1 , wherein said biological sample is saliva, whole blood, plasma, serum, or urine of a patient. 
     
     
         5 . The method according to  claim 4 , wherein said biological sample is plasma or serum. 
     
     
         6 . The method according to  claim 1 , wherein said measured level of said metabolites predicts the development of organ failure. 
     
     
         7 . The method according to  claim 6 , wherein said organ is liver, brain or kidney. 
     
     
         8 . The method according to  claim 6 , wherein an increased level of pentose phosphates, 2-Heptanone, N-Formyl-L-methionine, D-Threitol, N-Acetyl-L-aspartic acid, D-Galacturonic acid or p-Hydroxyphenyllactic acid is indicative of liver failure. 
     
     
         9 . The method according to  claim 6 , wherein an increased level of Methylimidazoleacetic acid, Guanidinosuccinic acid, N-Formyl-L-methionine, N-Acetyl-L-tyrosine or N-Acetyl-L-aspartic acid is indicative of brain failure. 
     
     
         10 . The method according to  claim 6 , wherein an increased level of 2-Heptanone, Trisaccharides, Cystathionine, Mevalonic acid, Octanoylcarnitine or p-Hydroxyphenyllactic acid is indicative of kidney failure.